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With a focus on learning, we employ a range of strategies to support innovation, collaboration across centers, and university-wide discussion and decision-making

 

Fifth Annual Grant Winners 2004-2005

Ling Li, Ph.D., HPD – College of Dental Medicine
Xudong Yuan, Ph.D., HPD – College of Pharmacy

Dean Robert Uchin, HPD – College of Dental Medicine
Dean William Hardigan, HPD – College of Pharmacy

Title: Targeted Gene Silencing by Small RNA Interference: Development of a Novel Delivery Method

Abstract:

One of key aspect of gene therapy is able to targeted reduce or silence the expression of deleterious genes, such as cancer or pain causing genes. RNA interference (RNAi) induced by small interfering RNA (siRNA) can lead to highly specific and extraordinarily efficient degradation of the corresponding mRNA, thus suppressing the targeted gene expression. However, advances in the areas of delivery, systemic spreading and duration of the silencing are necessary before the technology can enter clinical phase. The common used methods for delivery of siRNA are liposome and viral vector systems. The liposome deliver system is powerful in some cell lines. However, in most cell lines and mammalian tissues, the delivery efficiency is low and the duration of the silencing effect is short, lasting ~3 days. The pantropic retroviral vector can delivery siRNA into most of cell lines and mammalian tissues. However, the reverse transcription of the retroviral vector has introduced mutations into siRNA, attenuating the silencing effect. Recently, biocompatible and biodegradable polymeric microparticles and nanoparticles have been studied for the delivery of drugs to obtain enhanced therapeutic efficacy, prolonged half-life and reduced systemic side effect [For reviews, see (Cui and Mumper, 2003; Emerich and Thanos, 2003; Panyam and Labhasetwar, 2003; Vijayanathan et al., 2002)].

Therefore, we hypothesize that the new delivery system, nanoparticulate drug delivery system may be an efficient method to deliver siRNA , achieving high efficiency and long duration of silencing effect. Using Green Fluorescent Protein and its known efficient siRNA as a model system, we will compare the efficiency and duration of our new delivery system with the conventional liposome and retroviral delivery system. The efficiency and duration of the silencing effect will be determined by the inhibition of the green fluorescent protein expression using a fluorescent microscope equipped with a digital imaging system. The completion of this study will contribute to the long-term goal of developing targeted gene therapy system.